Abstract

Rationale

The hyperphagic effect of ∆9-tetrahydrocannabinol (∆9THC) in humans and rodents is well known. However, no studies have investigated the importance of ∆9THC composition and any influence other non-∆9THC cannabinoids present in Cannabis sativa may have. We therefore compared the effects of purified ∆9THC, synthetic ∆9THC (dronabinol), and ∆9THC botanical drug substance (∆9THC-BDS), a ∆9THC-rich standardized extract comparable in composition to recreationally used cannabis.

Methods

Adult male rats were orally dosed with purified ∆9THC, synthetic ∆9THC, or ∆9THC-BDS, matched for ∆9THC content (0.34–2.68 mg/kg). Prior to dosing, subjects were satiated, and food intake was recorded following ∆9THC administration. Data were then analyzed in terms of hourly intake and meal patterns.

Results

All three ∆9THC substances tested induced significant hyperphagic effects at doses ≥0.67 mg/kg. These effects included increased intake during hour one, a shorter latency to onset of feeding and a greater duration and consumption in the first meal. However, while some differences in vehicle control intakes were observed, there were significant, albeit subtle, differences in pattern of effects between the purified ∆9THC and ∆9THC-BDS.

Conclusion

All ∆9THC compounds displayed classical ∆9THC effects on feeding, significantly increasing short-term intake whilst decreasing latency to the first meal. We propose that the subtle adjustment to the meal patterns seen between the purified ∆9THC and ∆9THC-BDS are due to non-∆9THC cannabinoids present in ∆9THC-BDS. These compounds and other non-cannabinoids have an emerging and diverse pharmacology and can modulate ∆9THC-induced hyperphagia, making them worth further investigation for their therapeutic potential.

Keywords

Cannabis Phytocannabinoids Feeding ∆9THC Dronabinol Behavior

Abbreviations

2-AG

2-Arachidonoylglycerol

∆9THC

∆9-Tetrahydrocannabinol

∆9THC-BDS

∆9-Tetrahydrocannabinol botanical drug substance

∆9THCA

∆9-Tetrahydrocannabinolic acid

∆9THCV

∆9-Tetrahydrocannabivarin

AEA

Anandamide

ANOVA

Analysis of variance

CB1R

Cannabinoid type 1 receptor

CB2R

Cannabinoid type 2 receptor

CBC

Cannabichromene

CBD

Cannabidiol

CBG

Cannabigerol

CBN

Cannabinol

CBO

Cannabitriol

CNS

Central nervous system

eCB

Endocannabinoid

GPCR

G-protein coupled receptor

TRPA1

Transient receptor potential A1

TRPV1

Transient receptor potential vanilloid 1

This research was supported in part by the University of Reading Research Endowment Trust Fund (to JAF).

Notes

Acknowledgements

This research was supported in part by the University of Reading Research Endowment Trust Fund (to JAF). The authors thank Mr. Trevor Jenkinson and his team for technical assistance and GW Pharmaceuticals for the kind gifts of purified ∆9THC and ∆9THC-BDS.

Ethical compliance

All procedures were performed in compliance with the requirements of the United Kingdom Animals (Scientific Procedures) Act 1986 and all other applicable laws and standards in the U.K.